What are the recommended antibiotics for community-acquired pneumonia (CAP) in a patient with a penicillin allergy?

Community-Acquired Pneumonia Antibiotic Selection in Penicillin-Allergic Patients

For penicillin-allergic patients with community-acquired pneumonia, a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) is the preferred first-line monotherapy for both outpatient and hospitalized patients, with macrolides (azithromycin or clarithromycin) reserved only for outpatients without comorbidities in areas with macrolide resistance <25%. 1

Outpatient Management

Previously Healthy Patients Without Comorbidities

• A respiratory fluoroquinolone is the preferred option: levofloxacin 750 mg once daily for 5 days OR moxifloxacin 400 mg once daily for 7-10 days 1, 2
• Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for days 2-5) is acceptable ONLY if:
  • No recent antibiotic use within 3 months 3
  • Local macrolide-resistant S. pneumoniae prevalence is <25% 1, 3
  • No comorbidities (COPD, diabetes, renal failure, heart failure, malignancy, age >65 years, alcoholism, asplenia, immunosuppression) 3
• Doxycycline 100 mg twice daily for 7-10 days is an alternative option 1

Patients With Comorbidities or Risk Factors

• Respiratory fluoroquinolone monotherapy is strongly recommended: levofloxacin 750 mg daily or moxifloxacin 400 mg daily 1
• Avoid macrolide monotherapy in this population due to inadequate coverage of resistant S. pneumoniae and higher risk of treatment failure 3

Hospitalized Patients (Non-ICU)

• Respiratory fluoroquinolone monotherapy is the treatment of choice: levofloxacin 750 mg IV/PO daily or moxifloxacin 400 mg IV/PO daily 1
• The 2019 ATS/IDSA guidelines explicitly state that "a respiratory fluoroquinolone should be used for penicillin-allergic patients" in the hospital setting 1
• Duration: Minimum 5 days for levofloxacin 750 mg regimen, or 7-10 days for standard dosing 1, 2
• Oral administration is as effective as IV therapy and can be used from the start if no contraindications to oral intake exist 1, 4

Severe CAP (ICU Patients)

For penicillin-allergic patients with severe CAP requiring ICU admission:

• Respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) PLUS aztreonam (1-2 g IV every 8 hours) 1
• This combination provides coverage for both typical and atypical pathogens while avoiding β-lactam exposure 1
• Duration: 10-14 days, extended to 14-21 days if Legionella, Staphylococcus aureus, or gram-negative enteric bacilli are suspected or confirmed 1

Special Considerations for Severe CAP

• If MRSA is suspected: Add vancomycin 15-20 mg/kg IV every 8-12 hours or linezolid 600 mg IV every 12 hours 1
• If Pseudomonas aeruginosa is suspected: Use levofloxacin 750 mg IV daily PLUS an antipseudomonal agent (aztreonam 2 g IV every 8 hours, or an aminoglycoside) 1

Pediatric Patients (≥5 Years Old)

• Azithromycin: 10 mg/kg day 1 (max 500 mg), then 5 mg/kg daily days 2-5 (max 250 mg) 1, 5
• Clarithromycin: 15 mg/kg/day in 2 divided doses (max 1 g/day) 1
• Doxycycline (for children >7 years): 100 mg twice daily 1
• Levofloxacin (for children who have reached growth maturity or cannot tolerate macrolides): Use with caution due to musculoskeletal concerns 1

Critical Pitfalls to Avoid

Macrolide Resistance Issues

• Do NOT use azithromycin monotherapy if the patient received antibiotics in the past 3 months, as this selects for resistant organisms 3
• In regions with macrolide-resistant S. pneumoniae ≥25%, macrolide monotherapy has unacceptably high failure rates 1, 3
• Clinical failures with macrolide-resistant isolates occur in 20-30% of cases, often requiring hospitalization and β-lactam rescue therapy 3

Fluoroquinolone Safety Concerns

• Screen for cardiac risk factors and obtain ECG before initiating fluoroquinolones in patients with arrhythmia history 1
• Avoid fluoroquinolones in patients with history of tendon disorders, peripheral neuropathy, or myasthenia gravis 1
• Despite FDA warnings about adverse events, fluoroquinolones remain justified for CAP due to excellent efficacy, low resistance rates, and relative rarity of serious adverse events in this indication 1

Type of Penicillin Allergy Matters

• For patients with non-severe, questionable penicillin allergy history: Consider cephalosporins (cefpodoxime, cefprozil, or cefuroxime) under medical supervision, as cross-reactivity is <3% 1
• For patients with documented severe IgE-mediated reactions (anaphylaxis, angioedema, severe rash): Absolutely avoid all β-lactams including cephalosporins 1

Duration of Therapy

• Minimum treatment duration: 5 days for levofloxacin 750 mg regimen, with patient afebrile for 48-72 hours and no more than one sign of clinical instability 1, 3
• Do NOT extend therapy beyond 8 days in responding patients unless specific pathogens (Legionella, S. aureus, gram-negative bacilli) are identified 1, 3

Monitoring and Follow-Up

• Clinical review at 48 hours or earlier if clinically indicated 1
• Repeat chest radiograph at 6 weeks for patients with persistent symptoms, smokers, or those >50 years old 1
• Switch criteria from IV to oral: Clinical improvement, hemodynamic stability, ability to take oral medications, and functioning GI tract 1